title: Reversal of chemosensitivity and induction of cell malignancy of a non-malignant prostate cancer cell line upon extracellular vesicle exposure.
abstract: BACKGROUND
  Extracellular vesicle (EV) trafficking is a fundamental cellular process that occurs in cells and is required for different aspects of pathophysiology. EV trafficking leads to changes in cellular function including apoptosis, angiogenesis and proliferation required for increased tumor formation.
  
  
  RESULTS
  We report several phenotypic changes mediated by EVs isolated from non-malignant and malignant prostate cells as well as patient biopsied prostate tumor samples. EVs can reverse the resistance of prostate cancer cells to camptothecin EVs isolated from non-malignant PrECs (Prostate Epithelial Cells) can reverse soft agar colony formation of malignant DU145 cells, with the reciprocal effect observed. Isolation of EVs from 2 Gleason grade 8 prostate cancer patients significantly induced soft agar colony formation of non-malignant PrECs. We have identified proteins via antibody and Mass spectrometry analysis that may be responsible for the phenotypic changes. Mass spectrometry analysis of protein lysates using ProteoIQ revealed protein candidates associated with gene ontology annotations that may be responsible for this phenotypic change. Ingenuity Pathway Analysis was used to identify statistically relevant canonical pathways and functions associated the protein IDs and expression values obtained using ProteoIQ. Western blot analysis confirmed the increase of 14-3-3 zeta, pRKIP and prohibitin protein levels in PrEC cells co-cultured with patient EVs. 14-3-3 proteins were also found as common proteins of 3 other Gleason grade 8 patients.
  
  
  CONCLUSIONS
  Our study provides a rational basis to further investigate putative proteins, such as 14-3-3 and prohibitin and genetic factors that may be responsible for phenotypic changes that are associated with prostate cancer progression.
authors.affiliation: Division of Hematology/Oncology and Department of Medicine, Rhode Island Hospital, Providence, RI, USA. devasis_chatterjee@brown.edu.
authors.forename: Kiriaki
authors.initials: K
authors.lastname: Panagopoulos
authors.forename: Sam
authors.initials: S
authors.lastname: Cross-Knorr
authors.forename: Christen
authors.initials: C
authors.lastname: Dillard
authors.forename: Dionysios
authors.initials: D
authors.lastname: Pantazatos
authors.forename: Michael
authors.initials: M
authors.lastname: Del Tatto
authors.forename: David
authors.initials: D
authors.lastname: Mills
authors.forename: Lisa
authors.initials: L
authors.lastname: Goldstein
authors.forename: Joseph
authors.initials: J
authors.lastname: Renzulli
authors.forename: Peter
authors.initials: P
authors.lastname: Quesenberry
authors.forename: Devasis
authors.initials: D
authors.lastname: Chatterjee
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002166:Camptothecin / Q000494:pharmacology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D018920:Coculture Techniques; D019008:Drug Resistance, Neoplasm; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D060787:Neoplasm Grading; D010641:Phenotype; D010750:Phosphoproteins / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D020543:Proteome / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D022142:Secretory Vesicles / Q000502:physiology*; D015398:Signal Transduction; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; D018836:Inflammation Mediators; D010750:Phosphoproteins; D020543:Proteome; C106644:SOCS3 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D002166:Camptothecin